Lecture 9,10,11 Chronic Kidney Disease Flashcards
(54 cards)
Difference between CKD and end-stage renal disease?
CKD: abnormalities of kidney structure of fxn present for >3 months with implications on health, usually assessed by urine albumin (ACR) and GFR but also other markers
End-stage renal disease: state of renal failure where the metabolic disturbances are severe enough where kidneys can no longer fxn on their own, necessitates renal replacement therapy (ex. dialysis)
What are the classifications of CKD (KDIGO 2024)?
C - cause
G - GFR category ⇒ G1: kidney damage with normal or increased GFR, GFR > 90 ml/min/1.73m^2
G2: kidney damage with mild decrease in GFR, GFR 60-89 ml/min/1.73m^2
G3A/B: moderate decrease in GFR, G3A: GFR 45-59 ml/min/1.73m^2, G3B: GFR 30-44 ml/min/1.73m^2
G4: severe decrease in GFR, GFR 15-29 ml/min/1.73m^2
G5: kidney failure/end-stage renal disease, GFR < 15 ml/min/1.73m^2 or dialysis
CKD defined as either kidney damage or GFR < 60 for > 3 months
A - albuminuria category ⇒ via Albumin:Creatinine ratio (ACR): A1: ACR <3.0 mg/mmol (normally-mildly increased), A2: ACR 3.0-30 mg/mmol (moderately increased), A3: ACR > 30 mg/mmol (severely increased)
What are major causes of CKD?
diabetes mellitus (#1), HTN (#2), glomerulonephritis (#3), chronic interstitial nephritis, polycystic kidney disease, vasculitis, neoplasms, other
#1 and 2 account for around 55-70%, with CVD being the leading cause of mortality
What is it that HTN and diabetes actually leads to in CKD?
causes glomerulosclerosis (scarring) which equals a loss of nephron mass, glomerular HTN, and proteinuria
HTN causes increased RAAS systemic activation
What is the role of AGII?
enhances vascular tone (vasoconstricts) of both afferent and efferent arterioles, increases hydrostatic pressure, increases glomerular permeability, increased filtration of plasma proteins (albuminuria), excessive tubular reabsorption, renal scarring
What kind of effects does AGII have on the glomerular membrane?
it modulates renal cell growth ⇒ leads to tubulo-interstitial injury ⇒ structural damage, inflammation and fibrosis
How does diabetic nephropathy affect the kidneys?
glomerular hyperfiltration, altered glomerular composition, renal hypertrophy, glomerular HTN, proteinuria (ex. albuminuria) ⇒ all contributes to glomerular scarring
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What are progression factors in CKD?
hyperglycemia, HTN, smoking, obesity, proteinuria
Proteinuria in CKD
presence of protein in urine
Persistent = marker of kidney damage & indicator of renal disease
strong risk factor for CV mortality and morbidity
degree correlates to disease progression
Higher = higher risk of ESRD
Pathway: glomerular dysfunction ⇒ glomerular hyperfiltration ⇒ alters permeability of glomerular basement membrane (GBM) which is responsible for restricting protein filtration normally ⇒ leads to albuminuria ⇒ contributes to progressive nephron damage ⇒ filtered proteins reabsorbed by proximal tubular cells ⇒ ultrafiltered proteins activate inflammatory and fibrogenic pathways leading to further damage of interstitium and progressive loss of nephrons
Who is at risk for CKD?
Age (> 60), HTN, diabetes, family Hx, vascular disease, nephrotoxic drugs (NSAIDs, lithium), history of AKI, multisystem diseases with potential kidney involvement (lupus), health disparity
S&S of CKD
General: fatigue, edema, decreased urine output
Cardiac: HTN, HF, pericarditis, atherosclerosis, anemia
Dermal: pruritis
GI: anorexia, N/V, altered taste, constipation, bleeding
Neuromuscular: restless leg syndrome, muscle cramps, impaired cognition, peripheral neuropathy, malnutrition, bone pain
can be asymptomatic in initial stages
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What does KDIGO recommend for lifestyle management/changes for CKD tx?
A. Exercise - moderate intensity physical activity for cumulative duration of 150 minutes per week or to level compatible with their CV and physical tolerance
B. Weight loss where required
C. Smoking cessation
D. Low sodium diet (<2000 mg/day), balanced diet key
E. Protein intake of 0.8 g/kg body weight/day in adults with CKD G3-G5
F. Limit alcohol intake < 2 standard drinks/day (reduce CV risk)
What is meant by a protein restriction for CKD patients?
may be recommended to adults not on dialysis ⇒ pt with >1 g/day of proteinuria despite optimal BP control with ACEi or ARB
avoid high protein intake (>1.3 g/kg/d) in adults with CKD at risk of progression
those at high risk of kidney failure may be put on a very low protein diet (0.3-0.4 g/kg/d) supplemented with essential aa or ketoacid analogs (up to 0.6 g/kg/d)
do not prescribe low/very low protein diets to metabolically unstable pt with CKD
do not implement in pt who are <80% IBW
avoid malnutrition, KDIGO recommends 0.8 g/kg/d in adults stage G3-G5 (not including dialysis pt)
What are the goals of pharmacological management for CKD?
BP control: <130/80 mmHg (diabetic) and <120/80 mmHg (non-diabetic)
glycemic control
avoid possible nephrotoxic drugs (ex. aminoglycosides, NSAIDs)
ACEi and ARBs for CKD (mech and benefits)
used in CKD especially those with proteinuria, initiate at low dose and titrate slowly up, optimize according to proteinuria and BP target, temporarily suspend tx in setting of acute illness (to prevent AKI)
use in diabetic pt unless contra, in non-diabetic pt if ACR > 3 mg/mmol and no contra
Mech: reduce intraglomerular HTN by blocking vasoconstrictive effect of AGII on efferent arterioles, reduce hyperfiltration, reduce/stabilize proteinuria
Benefits: reduce albuminemia, slow progression of nephropathy in albuminuric normosensitive pt, slow progression to ESRD, reduce risk of development of new diabetic nephropathy
ACEi: shown to reduce progression of diabetic nephropathy in albuminuric normosensitive pt with both T1 and 2 diabetes
ARBs: shown to delay time to dialysis in those with renal fx at baseline
How should ACEis and ARBs be monitored in CKD (AE as well)?
Monitor: has risk of AKI due to hemodynamic effect - clinical setting of acute volume depletion: dehydration, HF
hold in setting of AKI
Contra: pregnancy, bilateral renal artery stenosis, hx of angioedema
AE: ACEi - dry cough, angioedema (rare)
start with low dose and titrate - expect 25-30% increase in SrCl within 1-2 weeks (reversible), monitor creatinine and K+ (hyperkalemia) 1-2 weeks after initiation or dose increases then every 3-6 months
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What are options for the tx of proteinuria in CKD?
ACEi and ARBs drug of choice
non-dihydropyridine calcium channel blockers (verapamil or diltiazem) - not first line but some effectiveness
spironolactone may decrease this in carefully selected pts - caution for hyperkalemia
MOA of SGLT-2is
inhibit this (main site of filtered glucose reabsorption) in proximal renal tubules
reduces reabsorption of filtered glucose from tubular lumen = increased urinary excretion of glucose = reduces plasma glucose conc
additional reduction of Na+ reabsorption = increased delivery of Na+ to distal tubule = may lower pre/after load of heart and downregulate sympathetic activity
reduction of Na+ reabsorption = increase delivery Na+ to macula densa = restore glomerular feedback = reduction in kidney blood flow = decreased glomerular hyperfiltration = reduction in intra-glomerular pressure = decreased albuminuria ⇒ eGFR stability moving forward (thought to be useful in CKD tx)
SGLT-2i use in CKD and KDIGO recommendations for its use
reduce intraglomerular pressure in individuals with and without diabetes
reno-protective - slow progression of CKD
T2D + proteinuric CKD - progression to ESRD reduced by canagliflozin, empagliflozin and dapagliflozin
in pt with proteinuric CKD without T2D risk of kidney disease progression reduced by dapagliflozin
KDIGO: initiate SGLT-2i for pt (add on to ACEi or ARB) with T2D and CKD who have eGFR 20 mL/min per 1.73 m^2 or higher
once initiated reasonable to continue this even if eGFR falls below 20 mL/min
DO NOT INITIATE IN PT STARTING DIALYSIS
EMPA-REG OUTCOME Trial findings
empagliflozin in pt with T2D with high CV risk have shown renal benefits
pt population = CVD, T2D and eGFR 30 mL/min or higher
in addition to 14% reduction of main CV outcomes, 39% reduction in worsening kidney disease and slower rate of eGFR decline compared to placebo
CANVAS Program Trial findings
canagliflozin in high CV risk and T2D population
pt population = CVD, T2D and eGFR over 30 mL/min
in addition to 14% reduction of main CV outcomes, 40% reduction in worsening kidney disease,, increases in lower extremity amputation and fracture incidence were observed with canagliflozin in this trial
DAPA-CKD Trial findings
this trial highlights dapagliflozin reduced risk of among CKD pt regardless of diabetes status (pt with or without T2D) and eGFR cutoff 25 mL/min or higher
39% decline in risk of worsening kidney fx, onset of ESRD, or kidney-failure related death
risk of composite of a sustained decline in eGFR of at least 50%, ESRD, or death from renal or CV causes sig lower with dapagliflozin than placebo
Overall: reduced risks of kidney disease progression in pt with CKD with or without T2D
How should SGLT-2is be monitored and AEs?
Monitor: anticipate acute rise in SrCl and corresponding decrease in GFR with initiation (3-4 mL/min) ⇒ should stabilize after about 4 weeks, repeat testing and close follow-up recommended if eGFR declines more than 20-25% with drug initiation - dose reduction or discontinuation if eGFR drops by > 30%
AE: genital mycotic (yeast) infections > 10% - report S/S, UTIs <10%, increased urination and thirst, diabetic ketoacidosis <1% - more likely to occur during acute illness (HOLD), (SOB, extreme thirst, confusion, fatigue, lack of appetite, ab pain, N/V ⇒ all these seek medical attention ASAP
Non-steroidal mineralocorticoid receptor antagonist (MRA) use in CKD (drugs, KDIGO)
Drugs: spironolactone (steroidal) - previously had evidence for lowering proteinuria
Finerenone (new, non-steroidal) - 2 clinical trials showing efficacy at reducing CKD progress and CV events in pt with DM + CKD, demonstrated renal and CV benefits for pt with T2D, CKD and eGFR >25 mL/min/1.73 m^2
KDIGO: these can be added to RAASi (ACEi/ARB) and SGLT-2i in pt with persistent albuminuria (>/= 3 mg/mmol) and normal serum K+ in CKD + T2D pt with eGFR > 25 mL/min
